Possible new target in wound healing

Researchers from University of Pennsylvania’s School of Dental Medicine are investigating possible new target in wound healing: FOX01. The skin, the largest organ in the body, has many functions:  barrier protection, secretion, excretion etc. The skin is the first line of defense against bacteria, viruses and parasites , and thus it plays an important role in controlling infection. When the skin is injured, a cascade of events is triggered to restore the continuity of the skin layer.

In the wound – healing process many molecules take part and one of them is FOX01. It seems that this molecule is essential in healing wounds and could provide new therapeutic target for the treatment of skin lesions. A critical event in the healing process is the movement of keratinocytes, the cells that make up the outer layer of skin, the epidermis. Previous studies have shown that during wound healing , FOX01 level is increased but the researchers did not understand what is the role this molecule play. It was also shown that in cancer cells FOX01 interferes with cellular reproduction and promotes cell death.

To learn more about the role of FOX01 in wound healing, a team of researchers led by Dana Graves, a professor in Penn ‘s Department of Periodontics Dental Medicine, conducted a study on mice that lack this protein, FOX01. The goal was to observe the healing process in mice that lack FOX01 and in normal mice. Investigators believed that mice that lack this protein would have a slower healing process but in fact it was the exact opposite. In normal mice, the lesions were cured after one week, while the mice that lack FOX01 still had open wounds.

To find out more about the function of this molecule, researchers investigated the effect of reducing the level FOX01 on other genes involved in wound healing. It was discovered that the level of important factors such as TGF- ß1 is also reduced. When researchers added TGF- ß1 in cells that lack FOX01, they observed that the cells behave normally , which means FOX01 acts upstream of TGF-ß1 in healing wounds. Also, researchers have found that mice that lack FOX01 had increased oxidative stress, which is detrimental to wound healing .

According to Graves, FOX01 that behave differently in certain situations indicate that wound healing is due to microenvironment. When is highly activated, FOX01 promotes cell death, but when is moderately active, it does the opposite. “If you had a small molecule that increased FOX01 expression, you might be able to upregulate TGF-ß1 as well as protect against the oxidative stress associated with wound healing,” researchers said.